Is a supplement called methylene blue really the “magic bullet” proclaimed by a 19th-century Nobel-prize winner?
Methylene blue even made the World Health Organization’s List of Essential Medicines.
Methylene blue medicine was quite possibly the first modern medicine, and it’s now being used for all kinds of off-label health and performance benefits:
- Learning & memory
- Cognitive enhancement
- Mood lifting
- Immune support
- Neuroprotection
- Mitochondrial energy support
- Trauma and stress resolution
- Longevity & anti-aging
- Beauty
And much more.
Could this be the cheapest (forgotten) health-optimizing substance?
This unique medicine has all kinds of unique mechanisms and use cases. Despite the recognition and accolades, for years I wouldn’t touch the stuff. As you’ll learn below, that changed when high-quality vendors began stocking it.
In this post, we’ll review the science of how methylene blue works, its researched health & performance benefits, and everything you must know before buying methylene blue online.
What is Methylene Blue
Methylene blue (sometimes called methylthioninium chloride) is a bioactive substance that was first synthesized in 1876 by a German chemist as a dye for staining. Then in 1891, Paul Ehrlich, a Nobel-prize winner first used methylene blue to treat malaria. Making it the first man-made drug used by humans. When injected, he observed that it concentrated in the brain’s most damaged and diseased tissues. His research led Ehrlich to coin the phrase “Magic Bullet” in reference to Methylene Blue.
In the early 1900s, doctors used it as an antipsychotic and mood-boosting pharmacotherapy. Then, in the mid-20th century, prior to antibiotics, it became an effective antifungal, antiviral, and antibacterial agent. This led to its rise as an antifungal fish tank cleaner.
Next, let’s discuss the mechanisms of action behind how methylene blue works.
How it works
Despite about 140 years of study, scientists are still uncovering all the pathways methylene blue improves.
Here are some of methylene blue’s core modes of action:
- Cycles electrons. Dose-dependent effects. At high doses, it donates electrons. At low doses, methylene blue accepts electrons. Few substances do both
- Increases mitochondrial respiration (cellular metabolism)
- Inhibits Nitric Oxide (which is technically a free radical). Increasing Nitric Oxide actually worsens symptoms of depression.
- Inhibits acetylcholinesterase (the enzyme that breaks down ACH) at low doses, thereby increasing acetylcholine levels. Improving memory, alertness, attention, and drive
- Inhibits monoamine oxidase-A (MAO-A) reversibly but fully, and monoamine oxidase-B (MAO-B) partially. Increasing levels of melatonin, serotonin, histamine, and catecholamines like adrenaline, dopamine, and noradrenaline
- Increases ATP production by accepting electrons for the electron transport chain (ETC). Improving effectiveness of the energy generation process
- Stimulates mitochondrial NAD+ production. NAD+ is the cellular fuel for the sirtuin anti-aging proteins.
- Scavenges free radicals due to its antioxidant properties. This is another mechanism explaining its protective and longevity-enhancing powers
- Crosses the blood-brain barrier quickly and effectively
Many of these depend on the dose and method of use.
Forms of administration
How do people use MB? What are the core delivery mechanisms?
It’s sold in all kinds of forms:
- Methylene blue lotion
- Methylene blue IVs & intradermals
- Methylene blue concentrate
- Methylene blue oral liquid
- Methylene blue liposomes
- Methylene blue sublingual tablets
- Methylene blue suppositories
- Methylene blue skin cream & lotion
- Methylene blue toothpaste
Clinically, methylene blue is most often used intravenously (IV). It’s also sometimes injected intrademally.
Off-label use is usually oral, liquid methylene blue. Quality tablets and powders are rare. Solid powder forms are often sold as methylene blue trihydrate.
Methylene blue IVs and suppositories have awesome bioavailability and slow, extended-release.
Skin creams and lotions quickly turn blue when the products contain a therapeutic dose, making it not feasible.
Sublingual delivery doesn’t seem to have much additional benefit.
Oral delivery also works great. When it naturally mixes with stomach acid, that enhances its absorption.
After ingestion in any manner, methylene blue concentrates and protects the most metabolically active tissues (especially your organs).
Methylene Blue’s Health, Cognitive, & Performance Benefits
Methylene blue rapidly saturates tissues with the greatest need and crosses the blood-brain barrier to provide systemic effects.
Methylene blue has a wide variety of benefits:
- Metabolism & energy optimization
- Cognitive & memory enhancement
- Trauma & fear resolution
- Anti-aging & longevity
- Focus & attention
- Beauty & skincare
- Immune health
- Happy mood
And a whole lot more.
Low doses seem preferable for most off-label use,
“…low doses of MB produce maximum behavioral and biochemical responses with averages of approximately 140% of control. As MB dose is raised outside the hormetic zone the response decreases below the control response, as exemplified by MB’s ability to increase cytochrome oxidase activity at intermediate doses, while decreasing cytochrome oxidase activity at higher doses.”
Best of all, it has an incredibly low-risk profile, with the data showing both short-term and long-term safety.
Now, let’s dig into each of the use cases.
Methemoglobinemia
Methemoglobinemia is the only FDA-approved use for methylene blue.
This is a blood disorder that prevents optimal oxygen utilization. In methemoglobinemia, the body produces too much oxidized hemoglobin (methemoglobin).
Methemoglobinemia results in all kinds of dangerous symptoms. Luckily, it’s treatable with MB. Methylene blue converts methemoglobin into a better form, helping alleviate symptoms.
Poison antidote
One of methylene blue’s original uses was as an antidote to chemical poisonings. Particularly, carbon monoxide & cyanide poisoning.
In fact, if you show up at the hospital with either of these poisonings, the standard treatment is to administer a high-dose methylene blue IV.
It’s still one of the most effective antidotes available.
Cyanide and carbon monoxide impair the electron transport chain and shut down cellular energy generation. Methylene blue restores the electron transport chain’s function, as well as helps hemoglobin better transport oxygen.
Cognition
The nootropics and cognitive enhancement “neurohacker” community has an obsession with methylene blue.
This molecule appears to improve multiple facets of cognition. It increases levels of dopamine — the neurotransmitter of motivation and drive. Methylene blue increases cerebral blood flow and mitochondrial function which accelerates information processing speed.
Increasing cellular energy results in better brain function overall.
At the same time, it protects neurons from excess reactionary oxygen species (ROS) production and glutamate overexcitation.
A study titled, Methylene blue modulates functional connectivity in the human brain, found that it encourages abstract thinking and forming new perceptions.
Methylene blue also supports cognition by enhancing the formation of new neural pathways (neurogenesis) and the weakening of disserving trauma pathways.
Learning & memory
Methylene blue is a potent enhancer of learning and memory abilities. It works multiple ways.
It’s an acetylcholinesterase inhibitor, reducing the breakdown of acetylcholine and facilitating learning.
Methylene blue seems to improve short-term memory, memory consolidation, and long-term memory. Increased activity in complex IV of cytochrome c oxidase generates more ATP for the memory centers of the brain. Functional MRI scans confirm better short-term memory performance and retrieval.
Another of methylene blue’s cognitive modes of action is increasing brain cell respiration at low doses. That study concluded that improved brain oxygenation directly improved memory.
It also seems to reverse memory issues (ie forgetfulness) and cognition in patients with Alzheimer’s.
Fascinatingly, a study of aging mice found that methylene blue can even restore forgotten memories.
Methylene blue has fairly strong evidence of nootropic benefits for things like supporting neurogenesis, learning, and memory.
Neuroprotection
An important benefit of methylene blue is protecting the brain against damage. Helping mitigate degenerative conditions like Alzheimer’s and dementia.
It does this several ways.
First, by supplying cells with ample energy which prevents premature death.
Methylene blue has anti-amyloid beta plaque effects, inhibits tau protein tangles, and improves other biomarkers of neurodegeneration.
Additionally, methylene blue protects the brain during periods of inadequate oxygenation (such as during strokes).
During acute damage caused by excess reactive oxygen species (ROS), glutamate, and superoxide, MB can donate electrons and protect against neurotoxicity.
Methylene blue also can help offset microglia-induced neuroinflammation. Microglia are a special subset of immune cells that “fight” perceived threats. They do this by causing inflammation. Excess levels damage the brain and slow repair. Overactivation of these cells is a main factor making traumatic brain injury so dangerous. A study showed that methylene blue can normalize microglia and promote cellular cleanup.
Energy & metabolism
One of the core ways methylene blue confers so many benefits is through its ability to increase cellular energy (ATP) efficiency and capacity.
ATP is the energetic currency of life, and a dominant fuel powering virtually all biological processes. When ATP production falls, so do physical and mental performance and resilience against disease.
Methylene blue can insert itself where needed in the energy generation process (electron transport chain). Profoundly improving mitochondria and metabolic health.
It also can increase levels of a key longevity molecule called NAD+. Mitochondria use NAD+ as a substrate to generate ATP. High NAD+ is also associated with more energy — cellular, physical, and mental.
Longevity
Longevity is the science of slowing the biological aging process to improve healthspan. Methylene blue appears to have a variety of overlooked yet promising “anti-aging” benefits.
We’re still awaiting human studies measuring the healthspan results from supplementing methylene blue.
This compound appears to target and improve multiple tenants of aging.
Methylene blue activates vital longevity proteins called sirtuins which are key to maintaining maximum healthspan. This SIRT1 activation “…promotes mitochondrial biogenesis and oxygen consumption and activates AMPK, contributing to anti-lipogenesis in the liver”.
Resulting in a cleaner, more efficient metabolism.
Newer research suggests that methylene blue can upregulate the cellular recycling process called autophagy (AMPK and PPARα),
“…activates signaling pathways involved in the mitochondrial pool renewal (mitochondrial biogenesis and autophagy)”
It also helps protect the brain from neurodegeneration and dementia — which are strongly associated with decreased healthspan.
For more information on the promising link between methylene blue and longevity, check out this paper titled, The Potentials of Methylene Blue as an Anti-Aging Drug.
Anti-microbial
Since 2020, methylene blue has regained popularity due to its powerful anti-microbial, anti-pathogenic benefits.
Although it has an illustrious history of use as an infection-fighting drug. Back in 1891, methylene blue was first used to treat malaria.
Now, methylene blue is used against a wide variety of infections:
- Viruses
- Bacteria
- Fungi
- Malaria
- Hepatitis C
- MRSA (Methicillin-Resistant Staphylococcus Aureus)
- HIV
- Candida
- Psoriasis
Eventually, its use for certain conditions dropped as synthetic derivates like chloroquine entered the market.
It seems to work differently with each pathogen. In some, it causes mitochondrial dysfunction. In others, it deactivates nucleic acid production.
Current research is determining if combining it with antibiotics can prevent drug resistance.
Methylene blue’s ability to interfere with a wide range of pathogens has earned it a spot in my immune health stack.
Antioxidant
Oxidation is one of the key hallmarks of aging and a process responsible for gradually diminishing quality of life.
Antioxidants stop the process by donating an electron to unstable molecules which stops the cascade of damage.
Methylene blue binds to an oxidant called superoxide and converts it into water. Stopping widespread damage.
Since it can cross the highly selective blood-brain barrier, this is one of few substances that can quell this same oxidative cascade occurring in the brain.
Additionally, methylene blue can upregulate the body’s built-in antioxidant defense (NRF2) system.
Its antioxidant properties are one of the primary features that make it such an effective substance.
Mood
Methylene blue promotes optimism and an uplifted mood. Even low-dose MB has antidepressant and anti-anxiety effects, but safer than most conventional options.
Like traditional medications, methylene blue inhibits both MAO-A (primarily) and MAO-B (less). Large doses inhibit both. These MAOs (dopamine, melatonin, and serotonin) are responsible for breaking down neurochemicals associated with mood.
According to traditional theory, inhibiting them results in increased optimism and antidepressant effects as confirmed by this paper,
“…methylene blue produced an antidepressant and anxiolytic effect without risk of a switch into mania. Long-term use of methylene blue in bipolar disorder led to a better stabilization and a reduction in residual symptoms of the illness.”
Meaning that methylene blue also reduced anxiety without the consequences bipolar patients face when using their normal medications.
Indeed, it’s working so well that researchers have been branching out to explore other compounds structurally similar to methylene blue.
Shock
Septic shock occurs when blood pressure drops dangerously low (hypotension). This impairs necessary blood flow to organs, including the brain).
Left untreated, shock can be fatal. Methylene blue can correct blood pressure issues, regardless of cause. One related example, is vasoplegic syndrome. A rare complication of heart surgery, vasoplegic syndrome destabilizes blood pressure.
Typically, vasopressors are the class of medication used to treat hypotension.
Ample data show methylene blue effectively counteracts hypotension from both septic shock and related conditions. In all instances, improving blood pressure.
If medication is needed, co-administering methylene blue can reduce the necessary dose of vasopressors.
Fear & trauma
Methylene blue may help users process and rid previous traumas.
PTSD is a condition in which the body constantly relives a previous stressful experience. It gets “stuck” in that loop. Beginning in 2004, researchers began investigating how methylene blue can help.
These studies revealed that when taken after a successful therapy session, methylene blue helped remove the harmful memories causing stress loops.
Follow-up trials came to the same conclusions.
Just make sure to use it only after successful sessions.
Hormonal optimization
Methylene blue does have an impact on the endocrine system.
Although there isn’t a large body of research investigating these properties yet, I managed to dig up a little.
Here is how methylene blue impacts hormones:
- Increases T4 thyroid hormone
- Decreases prolactin
- Antagonizes estrogen
A study of mice with testicle damage showed that increased their testosterone levels.
Skin health
Methylene blue has a budding role as a skincare ingredient.
In fact, these blue-colored substances are becoming quite popular in skin creams, lotions, and products. Both the fantastic peptide GHK-Cu, and now methylene blue protect and restore the skin.
That’s because the antioxidant properties of MB protect the skin from damaging UV rays, while simultaneously building healthy connective tissue better than other common antioxidants.
It also seems to slow the process of cell death while improving skin proteins of youthfulness like collagen and elastin.
That study suggested that methylene blue benefits skin via:
- Improved skin viability
- Promoted wound healing
- Increased skin hydration
- Increased dermis thickness
Intradermal injection can also help treat burns and reduce the progression of necrosis.
The primary issue with methylene blue in skincare products is that it’s extremely difficult to get a therapeutic dose without turning the contents neon blue!
Athletic performance
No studies have directly examined how methylene blue impacts physical/sports performance.
Some of the mechanisms discussed previously should support athleticism:
- Increased catecholamines from the MAOI
- Increased energy and endurance from mitochondrial enhancement
- Increased recovery from the antioxidant properties
- Increased memory and decision making
This is hypothetical since MB’s ergogenic benefits have not been studied specifically.
It could also protect the immune system during periods of overtraining/under-recovery. Overall, however, methylene blue wouldn’t be the star peri-workout supplement.
Using Methylene Blue
I get a lot of questions about how to best use methylene blue. The ideal methylene blue protocol.
It’s relatively straightforward, and the first step is to get the highest quality product possible (more on that later).
Your next consideration is your use case. Optimal methylene blue dosage depends on the benefits you’re targeting.
I avoid taking it daily to avoid over-sanitizing my microbiome (the anti-microbial effects are strong).
There are a few minor side effects to know about, and contraindications for use. More on all that now.
Dosage & protocol
Dosing varies tremendously.
Human doses of methylene blue range from 0.02mg to 100mg+.
Yes, a 5000X difference between the two extremes.
Most people using methylene blue off-label use 1-10mg.
This would be considered a micro-dose. Most studies use 1 – 4mg per kilogram of body weight. Say I weigh 90 kg, that would equate to 90 – 360mg! Note that in doses exceeding about 4mg per kg, MB becomes a pro-oxidant.
Dr. John Lieurance uses 40-80mg with most of his patients. And even higher doses when they’re sick.
Daily use is not problematic, but it can cause a buildup in mitochondria. You’ll know you need a break when you start feeling fatigued. Several days off is fine.
An ideal methylene blue protocol would look like this:
- 1-40mg oral dose (with a preference towards ~5-10mg)
- Taken in the morning
- 10 days on
- 3 day break
This is just one potential protocol, and I prefer low doses to minimize side effects.
Side effects
Since methylene blue works through multiple modes of action, it also has some side effects.
It’s also contraindicated for those that are pregnant, breastfeeding, or have a G6PD genetic deficiency. So if you match any of those, please avoid MB.
Common side effects include:
- High blood pressure
- Inaccurate pulse oximeter readings
- Abnormal urine color
- Abnormal stool color
Other potential side effects include:
- Mild bladder irritation
- Dizziness
- Headache
- Increased sweating
- Nausea
- Vomiting
- Abdominal pain
- Diarrhea
- Upset stomach
- Frequent urination
- Stomach cramps
How to Buy The Highest-Quality Methylene Blue Online
Before buying methylene blue, I did a ton of research. Quality matters more than most supplements.
You can buy pure methylene blue as powder, liquid, or tablets. Some companies even sell liposomal methylene blue, but that’s not worth the extra cost because the normal oral form is very bioavailable.
Although it is available legally over the counter, I recommend avoiding methylene blue sold on Amazon. Amazon is known to allow third parties to fraudulently sell counterfeit and/or questionable quality supplements.
Methylene blue is sold in different purities:
- Pharmaceutical-grade
- Industrial/chemical-grade
- Textile-grade
Even products appearing to be high-quality can contain toxicants like arsenic, aluminum, lead, cadmium, and mercury.
In fact, industrial-grade methylene blue can contain up to 11 percent heavy metals and other contaminants! Chemical suppliers regularly warn customers that non-USP methylene blue is not for human consumption.
You want to find a high-quality, pharmaceutical-grade product that’s at least USP39.
I’ve only found three sources of reliably pure methylene blue:
I am sure there are others, but these are the ones I am familiar with.
My Experience Using Methylene Blue
Over the years, I’ve likely used MB 100+ times.
I’ve tested all kinds of doses, ranging from 50 mcg – 50mg. For cognition and general effects, I prefer 5-10mg. I take this several times per week, but have also experimented with short-term daily use.
I like the liquid, as it is easiest to precisely dose (measuring out 0.5mg of powder is not for the faint of heart). If you buy powder, you’ll want to volumetrically dose it in liquid anyway. Whichever form you choose, major warning…
BE VERY CAREFUL. This stuff stains the heck out of anything it contacts. No amount of scrubbing, soap, or alcohol will remove these blue patches.
I find it works nicely to add the desired number of drops into a drink and then gulp it down through a straw. That’s an easy way to minimize the blue tongue, teeth, and lips.
Regardless of the dose, I notice only slight effects. I certainly don’t feel like I do while on my favorite nootropic products.
After about 30 minutes, I notice the effects kicking in. Primarily, a slight uplifting of mood. An hour in, words come to me easier. I feel more verbally fluent. I find that I am able to get more creative work done, faster.
I don’t feel any intense surges of energy, perhaps because I use a number of different energy-boosting technologies & tips.
The first time I used it, ~12 hours later I was startled by the blueish-green pee side effect. Yep, it is real.
Methylene Blue Alternatives & Stacks
Methylene blue is fantastic and powerful on its own.
Savvy biohackers, however, combine it with other things for a massive upgrade.
Red light therapy. The most popular methylene blue stack is actually a modality called photodynamic therapy. Both red light and MB improve mitochondrial performance and boost ATP generation but through different mechanisms. Together, they’re great for brain health (BDNF), DNA protection & repair, and cellular rejuvenation.
This can also work with infrared-light-rich sun exposure during sunrise and sunset. For an extra boost, combine with Chlorella, Chaga, mushrooms, or Shilajit.
Blue Cannatine. If you’re more interested in the cognitive performance capabilities of MB, this is a thoroughly formulated stack that’s both powerful and balanced. Dr. Ted Achacoso combined methylene blue, caffeine, nicotine, and hemp crystals into a special delivery mechanism called a troche. Blue Cannatine is one of my favorites for deep work sessions.
Silver or gold. Dr. John Lieurance uses methylene blue in his clinic more than anyone I’ve heard of. So much that he wrote a book on it. He says that compounding MB with either of these metals increases its photodynamic aspect.
Other alternatives. Depending on your goals and background, certain nootropics or mitochondrial enhancers might work better. If I am missing something, let me know in the comments!
Tips to boost the benefits of your Methylene Blue
Nootropics aren’t cheap.
You can skip this entire section, but these tips will help ensure that you get the most out of your experience.
Caffeine-free. If you’re new to nootropics, start with the non-caffeinated versions. I drink coffee most days. Sometimes two cups. But I always get my nootropics caffeine-free. For several reasons. First, nootropics potentiate caffeine. One coffee can feel like 3. If you’re not used to the combo, going caff-free gives you more control. Caff-free also means that I can take nootropics later in the day. Also, the health benefits of coffee don’t come from caffeine but from the polyphenols, flavonoids, and other phytochemicals. Plus, I just like the taste of coffee.
DNA decoded. Every human has profound uniquenesses. Even more so, in the brain. My favorite ingredients might give you migraines, and vice-versa. By taking a ~$50 once-in-a-lifetime test and running it through the powerful SelfDecode genetic software, you can easily understand your neurodiversity. To figure out what will work for your brain specifically. Without wasting time, energy, and money on ineffective (or even harmful) nootropics.
Optimal fuel. Nootropics love dietary fat. Certain fats, like a special extract of coconut called C8 MCT Oil, deliver some compounds into the brain more effectively. It also slows their absorption and metabolism. Resulting in a smoother and stronger nootropic experience (with even less crash).
Avoid kryptonite. If fat is a nootropic’s best friend, protein is the enemy. Now don’t get me wrong, I’m a huge advocate for consuming protein and aminos (especially essential amino acids). These aminos, however, compete with nootropics for absorption. If taken too close together, protein can reduce the effects you feel. A rule of thumb is to take nootropics at least 1 hour before eating or wait one hour after.
Optimize recovery. Nootropics are like the gas pedal for your brain. If you don’t recover (while sleeping), eventually you’ll burn out and they’ll lose their charm. There are many ways to improve your recovery. First, increase your sleep time and quality. Your brain needs some extra downtime to compensate for working so hard. Next, feed it the right nutrients. I feel a pronounced difference when I take Shilajit and Magnesium with my nootropics. I’m able to cut back my dose and still feel stronger effects.
If you like this kind of thing, join my FREE nootropics mini-course where you’ll learn:
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Methylene Blue Supplement: Final Verdict
Methylene blue was the first man-made drug, yet today it’s largely unknown.
Despite that, it’s on virtually every list of essential medicines and has wide-ranging use cases.
This is one powerful health optimization tool.
MB is one of few nootropics that not only increase performance but also build (and protect) health at the root level — mitochondria.
Quality methylene blue is hard to find online.
If I couldn’t get pure methylene blue, due to the off-the-charts contamination levels, I’d avoid it completely.
Interested in running your own experiments with “blue gold”?
Pick up a bottle by clicking the button below.
Use the exclusive SwissChems coupon code URBAN for 15% off
Do you use methylene blue? Let me know your experience in the comments below!
Methylene Blue Supplement
Methylene blue, also known as methylthioninium chloride, is a salt used as a dye and as a medication. It is used to treat methemoglobinemia by converting the ferric iron in hemoglobin to ferrous iron. This is a science-based review of Methylene Blue to help you learn more about the science behind this supplement and how it can benefit your health.
Product Brand: Methylene Blue
4.38
Pros
- Longevity & anti-aging
- Cognitive enhancement
- Afforadble
Cons
- Quality methylene blue is hard to find online.
Ask Nick a Podcast Question
Hi Nick,
What are your starting points for your calculations? 1-4 mg per kg body weight based on 1% solution or pure powder? It is common to make a solution in distilled water from 1 – 5%? I have seen a couple of interviews on YouTube with, among others, md tom rogers and getting even more confused…
PS Thanks for lots of inspiring material and good youtube interviews!
Hey Dag!
You’re right, methylene blue dosing is kinda tricky. 1-4mg per kg is based on a 1% solution. I personally usually just use a 5-20 milligrams for a slight nootropic effect. Dr. John Lieurance’s book Methylene Blue Magic Bullet is a great resource for everything you could want to know about this.
You’re welcome!
I am interested in the potential benefits of the Methylene Blue product. I am a male senior citizen, and don’t know if this will work for me?
I think your article is very well written and very informative. I like the thought of improved memory, focus, mood and energy. If this product will supply additional oxygen, it could improve my neuropathy.
Please sign me up for current and future articles that may improve my overall health.
Hey Doug! Thanks for that. I know that you left this comment nearly a year ago, but I’m curious if you ever ended up testing methylene blue. There are tons of sources and products available now. Did you make it on the Outliyr email newsletter? You can join by clicking here.